Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species
| Autor: | Amit Singh, Mansi Mehta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Iron-Sulfur Proteins Transcription Genetic Biosensing Techniques Biochemistry Redox Article Mycobacterium tuberculosis 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Physiology (medical) Peroxynitrous Acid Benzene Derivatives Animals Homeostasis Humans Transcription factor Reactive nitrogen species Nitrites chemistry.chemical_classification Microbiology & Cell Biology Reactive oxygen species Microbial Viability biology Gene Expression Regulation Bacterial Hydrogen Peroxide biology.organism_classification Reactive Nitrogen Species 3. Good health Cell biology 030104 developmental biology RAW 264.7 Cells chemistry Cumene hydroperoxide Host-Pathogen Interactions Leukocytes Mononuclear Reactive Oxygen Species Oxidation-Reduction 030217 neurology & neurosurgery Bacteria Peroxynitrite Gene Deletion Transcription Factors |
| Zdroj: | Free radical biology & medicine |
| ISSN: | 1873-4596 0891-5849 |
| Popis: | Mycobacterium tuberculosis (Mtb) survives under oxidatively and nitosatively hostile niches inside host phagocytes. In other bacteria, adaptation to these stresses is dependent upon the redox sensitive two component systems (e.g., ArcAB) and transcription factors (e.g., FNR/SoxR). However, these factors are absent in Mtb. Therefore, it is not completely understood how Mtb maintains survival and redox balance in response to reactive oxygen species (ROS) and reactive nitrogen species (RNS). Here, we present evidences that a 4Fe-4S-cofactor containing redox-sensitive transcription factor (WhiB3) is exploited by Mtb to adapt under ROS and RNS stress. We show that MtbΔwhiB3 is acutely sensitive to oxidants and to nitrosative agents. Using a genetic biosensor of cytoplasmic redox state (Mrx1-roGFP2) of Mtb, we show that WhiB3 facilitates recovery from ROS (cumene hydroperoxide and hydrogen peroxide) and RNS (acidified nitrite and peroxynitrite). Also, MtbΔwhiB3 displayed reduced survival inside RAW 264.7 macrophages. Consistent with the role of WhiB3 in modulating host-pathogen interaction, we discovered that WhiB3 coordinates the formation of early human granulomas during interaction of Mtb with human peripheral blood mononuclear cells (PBMCs). Altogether, our study provides empirical proof that WhiB3 is required to mitigate redox stress induced by ROS and RNS, which may be important to activate host/bacterial pathways required for the granuloma development and maintenance. |
| Databáze: | OpenAIRE |
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